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Long-term Renal Effects of Tenofovir-Disoproxil-Fumarate in Vertically HIV-Infected Children, Adolescents, and Young Adults: A 132-Month Follow-Up Study

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Abstract

Background and Objectives

The introduction of highly active anti-retroviral therapy has led to a significant decline in morbidity and mortality. Although several studies in adult populations have shown that tenofovir-disoproxil-fumarate (TDF) use is associated with a significant loss of renal function, there is still uncertainty on the long-term TDF safety profile in pediatric HIV populations, mostly in vertically HIV-infected patients. The aim of this study was to evaluate the long-term TDF renal safety profile, during a ten-year follow up.

Methods

Twenty-six vertically HIV-infected patients were evaluated for a total of 132 months of follow up, monitoring anthropometric parameters, renal function, viral load and CD4+ count. Generalized estimating equations were used to evaluate the changes in anthropometric and laboratory variables. Multivariable fractional polynomials were used to test for the existence of non-linear relationships of outcomes with time and other continuous covariates. In all patients, weight, height and body mass index increased linearly with time. CD4+ count and glomerular filtration rate decreased linearly with time (p < 0.01).

Results

No significant increase of serum creatinine was registered. An inverse linear relationship between time and plasma phosphate was found. Hypophosphatemia was detected in 17 patients, mostly mild. In 14 out of 17 we also genotyped single nucleotide polymorphisms rs717620 mapping in ABCC2, a gene encoding for a renal transporter.

Conclusions

Our study demonstrates the relative safety of prolonged use of TDF in vertically HIV-infected children and young adults. The most relevant alteration that emerged was hypophosphatemia, appearing after 72 months of TDF therapy, mostly mild and without clinical significance.

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Conflict of interest

The authors have indicated that they have no other conflicts of interest regarding the content of this article. No funding has been used in this study.

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Authors and Affiliations

  1. Pediatric Infectious Diseases Unit, L. Sacco Hospital, University of Milan, via G.B. Grassi 74, 20157, Milan, Italy

    Vania Giacomet, Pilar Nannini, Alessandra Vigano, Paola Erba & Annarita Benincaso

  2. Clinical Epidemiology Unit, Liver Research Center, Basovizza, Trieste, Italy

    Giorgio Bedogni

  3. Unit of Clinical Pharmacology, L. Sacco University Hospital, Milan, Italy

    Dario Cattaneo & Felicia Stefania Falvella

  4. Ospedale dei Bambini Vittore Buzzi, University of Milan, Milan, Italy

    Gian Vincenzo Zuccotti

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  1. Vania Giacomet
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  2. Pilar Nannini
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Correspondence to Vania Giacomet.

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Giacomet, V., Nannini, P., Vigano, A. et al. Long-term Renal Effects of Tenofovir-Disoproxil-Fumarate in Vertically HIV-Infected Children, Adolescents, and Young Adults: A 132-Month Follow-Up Study. Clin Drug Investig 35, 419–426 (2015). https://doi.org/10.1007/s40261-015-0293-7

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